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abatacept autoantibody

Odilia B J Corneth, Gwenny M P Verstappen, Sandra M J Paulissen, Marjolein J W de Bruijn, Jasper Rip, Melanie Lukkes, Jan Piet van Hamburg, Erik Lubberts, Hendrika Bootsma, Frans G M Kroese, And Rudi W Hendriks
OBJECTIVE: Bruton's tyrosine kinase (BTK) transmits crucial survival signals from the B cell receptor (BCR) in B cells. Pharmacological BTK inhibition effectively diminishes disease symptoms in mouse models of autoimmunity and, conversely, transgenic BTK overexpression induces systemic autoimmunity in mice. We investigated BTK expression and activity in human B cells in the context of autoimmune disease. METHODS: Using intracellular flow cytometry, we quantified BTK expression and phosphorylation in peripheral blood B cell subsets in patients with rheumatoid arthritis (RA; n=30) and primary Sjogren's Syndrome (pSS; n=26) and matched healthy controls...
January 31, 2017: Arthritis & Rheumatology
Carolin Wunderlich, Isabelle Oliviera, Camille P Figueiredo, Juergen Rech, Georg Schett
OBJECTIVE: To study whether stable treatment with DMARDs affects anti-CCP2 antibody levels in patients with rheumatoid arthritis. METHODS: In this longitudinal observational study 100 RA patients were followed for anti-CCP2 IgG antibody (U/L) and total IgG level (mg/dL) every 6 months for a total period of 2.5 years. All patients received stable DMARD treatment during this period. Five groups comprising each 20 patients were analyzed as follows: (1) methotrexate (MTX) alone, (2) tumor necrosis factor inhibitors (TNFi), (3) tocilizumab (TCZ), (4) rituximab (RTX), and (5) abatacept (ABA)...
October 3, 2016: Seminars in Arthritis and Rheumatism
M Cutolo, A Sulli, C Pizzorni, S Paolino, V Smith
<p>Systemic sclerosis (SSc) is characterized by autoantibody production, progressive microvasculopathy, and aberrant extracellular matrix protein (ECM) synthesis in tissues. The disease presents two major clinical hallmarks: Raynaud's phenomenon (RP) and skin involvement, followed by varying prevalences of internal organ involvement. Despite significant advances in the management of certain organ-specific involvements and symptoms, the research for efficient markers and targets, to be used for an optimized treatment, is still ongoing...
January 2016: Acta Reumatológica Portuguesa
Maurizio Cutolo, Alberto Sulli, Carmen Pizzorni, Sabrina Paolino, Vanessa Smith
Systemic sclerosis (SSc) is characterized by autoantibody production, progressive microvasculopathy, and aberrant extracellular matrix protein (ECM) synthesis in tissues. The disease presents two major clinical hallmarks: Raynaud's phenomenon (RP) and skin involvement, followed by varying prevalences of internal organ involvement. Despite significant advances in the management of certain organ-specific involvements and symptoms, the research for efficient markers and targets, to be used for an optimized treatment, is still ongoing...
February 17, 2016: Acta Reumatológica Portuguesa
Silvia Piantoni, Enrico Colombo, Angela Tincani, Paolo Airò, Mirko Scarsi
The aim of this paper was to look for predictors of abatacept (ABA) therapy discontinuation in patients with rheumatoid arthritis (RA). Seventy-one RA patients treated with ABA were followed up. Demographical, clinical, and laboratory parameters of the patients, including peripheral blood T and B cell populations, different rheumatoid factor and anti-cyclic citrullinated peptide autoantibodies isotypes, and serum free light chains were evaluated. Comparing patients who discontinued ABA with those still in therapy we observed: a higher proportion of smokers (51...
April 2016: Clinical Rheumatology
Elisa Astorri, Alessandra Nerviani, Michele Bombardieri, Costantino Pitzalis
Rheumatoid Arthritis (RA) is a chronic, inflammatory, autoimmune disease affecting diarthrodial joints and extra-articular tissues; in the absence of an effective treatment, it is characterized by persistent symmetrical and erosive synovitis which leads to structural joint damage and lifelong disability. Several autoantibodies have been associated with RA such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). B cells have been shown to play a crucial role in the pathogenesis of RA by producing autoantibodies and promoting synovial inflammation through antigen presentation, T cells activation and cytokines production [1]...
2015: Current Pharmaceutical Design
Martin Aringer, Josef S Smolen
INTRODUCTION: The approval of belimumab and other advances in the field have narrowed the window for off-label use of biologicals in systemic lupus erythematosus (SLE). For consideration in severe and refractory disease, safety will play a major role. AREAS COVERED: We reviewed the literature on safety aspects of off-label biological use in SLE. Significant evidence is available for rituximab, whereas data on the off-label SLE therapy with other biologicals are much more limited...
February 2015: Expert Opinion on Drug Safety
Melanie Gruner, Anja Moncsek, Stefan Rödiger, Dagmar Kühnhardt, Eugen Feist, Ralf Stohwasser
BACKGROUND: PA28γ (also known as Ki, REG gamma, PMSE3), a member of the ubiquitin-and ATP-independent proteasome activator family 11S, has been proved to show proteasome-dependent and -independent effects on several proteins including tumor suppressor p53, cyclin-dependent kinase inhibitor p21 and steroid receptor co-activator 3 (SCR-3). Interestingly, PA28γ is overexpressed in pathological tissue of various cancers affecting e. g. breast, bowl and thyroids. Furthermore, anti-PA28γ autoantibodies have been linked to several autoimmune disorders...
2014: BMC Musculoskeletal Disorders
Sarah Novotny, Kedra Wallace, Florian Herse, Janae Moseley, Marie Darby, Judith Heath, James Gill, Gerd Wallukat, James N Martin, Ralf Dechend, Babbette LaMarca
Similar to preeclamptic women, hypertension in the chronic Reduced Uterine Perfusion Pressure Rat Model Of Preeclampsia (RUPP) is associated with increased CD4(+) T cells, cytokines, sFlt-1 and agonistic autoantibodies to the AngII receptor (AT1-AA). We examined the effect inhibition of T cell co-stimulation in RUPP rats treated with (A) (abatacept, 250 mg/kg, infused i.v. at gestation day 13), on hypertension and sFlt-1, TNF-α and AT1-AA. RUPP surgical procedure was performed on day 14. On day 19 MAP increased from 94+2 mmHg in Normal Pregnant (NP) to 123 ± 3 mmHg in RUPP control rats...
June 17, 2013: Journal of Hypertension: Open Access
Lazaros I Sakkas, Dimitrios P Bogdanos, Christina Katsiari, Chris D Platsoucas
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein/peptide autoantibodies (ACPAs). Citrulline derives from arginine by peptidyl arginine deiminases, and ACPAs are directed against different citrullinated antigens, including fibrinogen, fibronectin, α-enolase, collagen type II, histones. ACPAs are present in two thirds of RA patients have higher specificity than RF for RA, and are associated with joint radiographic damage and extra-articular manifestations and they are detected years before the onset clinical arthritis...
November 2014: Autoimmunity Reviews
K Takase, S C Horton, A Ganesha, S Das, A McHugh, P Emery, S Savic, M H Buch
OBJECTIVE: To determine whether serial ANA testing predicts biological disease modifying antirheumatic drugs (bDMARD)-associated ANA/dsDNA production in patients with rheumatoid arthritis (RA). METHODS: Serial autoantibody profiles, bDMARD treatment sequences and clinical data were collected from patients identified from our database that since 2005 received (i) a first bDMARD (tumour necrosis factor inhibitor (TNFi)) and (ii) tocilizumab and/or abatacept. RESULTS: Of over 1000 patients, 454 RA patients received a first TNFi...
September 2014: Annals of the Rheumatic Diseases
Carlo Selmi
The peer-reviewed publications in the field of autoimmunity published in 2013 represented a significant proportion of immunology articles and grew since the previous year to indicate that more immune-mediated phenomena may recognize an autoimmune mechanism and illustrated by osteoarthritis and atherosclerosis. As a result, our understanding of the mechanisms of autoimmunity is becoming the paradigm for translational research in which the progress in disease pathogenesis for both tolerance breakdown and inflammation perpetuation is rapidly followed by new treatment approaches and clinical management changes...
August 2014: Clinical Reviews in Allergy & Immunology
Sulaiman M Al-Mayouf, Abdullatif Alenazi, Hind AlJasser
OBJECTIVE: To report the indications and safety of biologic agents in childhood rheumatic diseases at a tertiary hospital. METHODS: Children with rheumatic diseases treated with biologic agents at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, from January 2001 to December 2011 were included. All patients were reviewed for: demographic characteristics, diagnosis, concomitant treatment and indications of using biologic agents, age at start of therapy and side effects during the treatment period...
June 2016: International Journal of Rheumatic Diseases
Gregg J Silverman, Adam Pelzek
No abstract text is available yet for this article.
May 2014: Journal of Rheumatology
Mirko Scarsi, Lucia Paolini, Doris Ricotta, Antonio Pedrini, Silvia Piantoni, Luigi Caimi, Angela Tincani, Paolo Airò
OBJECTIVE: Abatacept (ABA) is a chimeric molecule, able to block the CD28-mediated costimulatory pathway. To evaluate the hypothesis that, through this mechanism of action, ABA may down-modulate the immune responses of B lymphocytes in rheumatoid arthritis (RA), we investigated the serum levels of immunoglobulins (Ig), free light chains (FLC), anticitrullinated protein antibodies (ACPA), and rheumatoid factor (RF), as well as the number of B lymphocytes differentiated into post-switch memory cells in patients treated with ABA...
April 2014: Journal of Rheumatology
Claire I Daïen, Jacques Morel
Many therapies are now available for patients with rheumatoid arthritis (RA) who have an inadequate response to methotrexate including tumor necrosis factor inhibitors, abatacept, tocilizumab, and rituximab. Clinical response to drugs varies widely between individuals. A part of this variability is due to the characteristics of the patient such as age, gender, concomitant therapies, body mass index, or smoking status. Clinical response also depends on disease characteristics including disease activity and severity and presence of autoantibodies...
2014: Mediators of Inflammation
Jennifer Pieper, Jessica Herrath, Sukanya Raghavan, Khalid Muhammad, Ronald van Vollenhoven, Vivianne Malmström
BACKGROUND: Rheumatoid arthritis is a chronic inflammatory disease with a strong MHC class II component and where many patients develop characteristic autoantibodies towards the noncoding amino acid citrulline. Such anti-citrullinated protein antibodies (ACPA) have recently been put forward as an independent predictive factor for treatment response by co-stimulation blockade by CTLA4-Ig (abatacept). We have performed a mechanism of action study to dissect T cell functionality in RA patients with long-standing disease undergoing abatacept treatment and the influence of ACPA status...
2013: BMC Immunology
Maurizio Cutolo, Steven G Nadler
Rheumatoid arthritis (RA) is a multifactorial and polygenic immune-mediated disease, the pathogenesis of which involves different cell types. T and B lymphocytes, macrophages, endothelial cells, fibroblasts and osteoclasts have all been implicated in mediating the production of autoantibodies, proinflammatory cytokines and ultimately bone erosions. Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA-4-Ig, abatacept) is a unique biologic agent targeting the co-stimulatory molecules CD80/CD86, and is indicated for the treatment of moderate-to-severe RA in patients who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs, including methotrexate or anti-tumor necrosis factor agents...
May 2013: Autoimmunity Reviews
J S Skyler
Since type 1 diabetes is an immunologically mediated disease, immune intervention should alter the natural history of the disease. This article reviews prevention studies undertaken either prior to any evidence of autoimmunity (primary prevention) or after the development of islet autoantibodies (secondary prevention). Most immune intervention studies have been conducted in recent-onset type 1 diabetes (tertiary prevention), and these are not reviewed herein. The goal of primary and secondary intervention is to arrest the immune process and thus prevent or delay clinical disease...
February 2013: Diabetic Medicine: a Journal of the British Diabetic Association
Saakshi Khattri, Gisele Zandman-Goddard, Elena Peeva
The increased awareness of the role of humoral immunophysiology in antiphospholipid syndrome (APS) has aroused interest in B cells as therapeutic targets in this disease. This paper reviews the literature on B cell directed therapies in human and experimental APS. The clinical data is limited to B cell depletion with rituximab and comprises case reports and case series. Murine studies include use of modulators of B cell function such as belimumab and abatacept. In both human and murine studies, B cell directed therapies appeared to have clinical and serologic beneficial effects including a decrease in the antiphospholipid antibody titers after treatment...
August 2012: Autoimmunity Reviews
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